Metoprolol is a beta-blocker that is prescribed for the treatment of hypertension, angina pectoris, and stable, symptomatic heart failure. Currently, the marketed extended-release dosage form of metoprolol succinate is a multiparticulate tablet dosage form comprising silicon dioxide beads as an inert core (Toprol-XL® tablet).
U.S. Pat. No. 5,246,714 discloses a controlled-release preparation containing a number of insoluble beads coated with one or more pharmaceutically active compounds. It further discloses examples of insoluble materials such as silicon dioxide, glass, or plastic resin particles.
In 2014, many generic metoprolol succinate extended-release tablets comprising multiparticulates were recalled from the U.S. market. As per the FDA Enforcement Reports, these tablets were recalled due to failed dissolution tests.
Compression of multiparticulates into a tablet dosage form is a challenging task. An additional 30% to 60% of tableting excipients are necessary to avoid any damage to the polymer coat and to retain the functional properties of the coat during compression. However, even after the process and excipient optimizations, cracks in the extended-release polymer coat are observed at the commercial scale. These cracks in the extended-release polymer coat impact the dissolution profile of the dosage form.
A capsule dosage form of coated multiparticulates offers an advantage over the tablet dosage form, as there is no compression step involved in capsule dosage forms. Further, this dosage form is easier to swallow and requires the addition of fewer excipients than the tablet dosage form.
Therefore, there is a need in the art to prepare an alternate extended-release dosage form of metoprolol succinate which is bioequivalent to the marketed Toprol-XL® tablet.